Title Lead Author Abstract # Presentation Location Date / Time ( CEST ) BAVENCIO(R) (avelumab) --- Poster Discussions --- Efficacy and biomarker analysis of the sarcomatoid subgroup from the phase 3 JAVELIN Renal 101 trial of first-line avelumab plus axitinib (A + Ax) vs sunitinib (S) for advanced renal cell carcinoma (aRCC) TK. Choueiri 4823 Sunday, September 29, 2019, 3:00-4:15 Hall 2 - Pamplona Auditorium PM Poster Board No. 910PD (3:15 PM lecture time) --- --- Primary renal tumour L. Albiges Sunday, September 29, 2019, 3:00-3:15 shrinkage in patients advanced renal cell PM (pts) who did not carcinoma (aRCC) undergo cytoreductive nephrectomy (CN): subgroup analysis from the phase 3 JAVELIN Renal 101 trial of first-line avelumab plus axitinib (A + Ax) vs sunitinib (S) for 4174 Hall 2 - Pamplona Auditorium (3:15 PM lecture time) Poster Board No. 908PD --- --- Poster Sessions --- Long-term avelumab Saturday, September 28, 2019, treatment in patients 12:00-1:00 PM with advanced non- small cell lung cancer (NSCLC): post-hoc analysis from JAVELIN Solid Tumor B. Hrinczenko 4256 Hall 4 -Poster Area Poster Board No. 1493P --- --- Assessing the impact of Saturday, September 28, 2019, subsequent 12:00-1:00 PM immunotherapy treatment on overall survival: a post-hoc analysis of the phase 3 JAVELIN Lung 200 study, 2L avelumab vs docetaxel in patients with platinum-treated NSCLC F. Barlesi 5113 Hall 4 - Poster Area Poster Board No. 1492P --- --- Randomized phase 3 trial Monday, September 30, 2019, 12:00-1:00 of avelumab + axitinib PM vs sunitinib as first- line treatment for advanced renal cell carcinoma: JAVELIN Renal 101 Japanese subgroup analysis M. Uemura 1451 Hall 4 - Poster Area Poster Board No. 956P --- --- Health-related quality Monday, September 30, 2019, 12:00-1:00 of life in patients PM with metastatic Merkel cell carcinoma receiving second-line or later avelumab treatment: 36-month follow-up data SP. D'Angelo 3152 Hall 4 - Poster Area Poster Board No. 1320P --- --- ERBITUX(R) (cetuximab) --- Poster Session --- Impact of primary tumor side on 3-year survival outcomes of first-line (1L) FOLFOX-4 +/- cetuximab in patients with RAS wild-type (wt) metastatic colorectal cancer (mCRC) in the phase 3 TAILOR trial S. Qin 4455 Sunday, September 29, 2019, Hall 4 - Poster Area 12:00-1:00 PM Poster Board No. 591P --- --- The cost of adverse Sunday, September 29, 2019, 12:00-1:00 event management in PM patients with RAS wild- type metastatic colorectal cancer treated with first- line cetuximab and panitumumab: an Italian healthcare payer perspective K. Patterson 1212 Hall 4 - Poster Area Poster Board No. 596P --- --- Non-inferiority on Sunday, September 29, 2019, 12:00-1:00 overall survival of PM every- 2-weeks vs weekly schedule of cetuximab for the first-line treatment of RAS wild-type metastatic colorectal cancer S. Kasper 2589 Hall 4 - Poster Area Poster Board No. 584P --- --- Tepotinib --- Poster Session --- Safety Profile of Saturday, September 28, 2019, Tepotinib in Patients 12:00-1:00 PM with Advanced Solid Tumors: Pooled Analysis of Phase I and II Data T. Decaens 3930 Hall 4 -Poster Area Poster Board No. 479P --- --- Drug-drug interaction Saturday, September 28, 2019, profile of tepotinib 12:00-1:00 PM with CYP3A and P-gp substrates J. Heuer 5373 Hall 4 - Poster Area Poster Board No. 480P --- --- Bioavailability of Saturday, September 28, 2019, tepotinib: impact of 12:00-1:00 PM omeprazole and food J. Heuer 5455 Hall 4 - Poster Area Poster Board No. 481P --- --- Combinations --- M6620 Oral Session --- Randomized Phase 2 Study of ATR inhibitor M6620 in Combination with Gemcitabine versus Gemcitabine alone in Platinum Resistant High Grade Serous Ovarian Cancer (HGSOC) PA. Konstantinopoulos 1547 Friday, Hall 2 - (NCT02595892) LBA60 September 27, 2019, 4:45-5:00 PM Pamplona Auditorium --- --- Poster Session --- Phase 1b, open-label, Monday, September 30, 2019, 12:00-1:00 dose-escalation study PM of M9241 (NHS-IL12) plus avelumab in patients (pts) with advanced solid tumors J. Strauss 4062 Hall 4 - Poster Area Poster Board No. 1264P --- --- Avelumab-cetuximab- Saturday, September 28, 2019, 8:45-9:45 radiotherapy versus AM standards of care in locally advanced squamous cell carcinoma of head and neck: safety phase of randomized trial GORTEC 2017-01 (REACH) Y. Tao 4934 Hall 5 -Bilbao Auditorium (9:05 AM lecture time) Poster Board No. 1118PD --- ---
About BAVENCIO(® )(avelumab)
BAVENCIO(®) is a human anti-programmed death ligand-1 (PD-L1) antibody. BAVENCIO(®) has been shown in preclinical models to engage both the adaptive and innate immune functions. By blocking the interaction of PD-L1 with PD-1 receptors, BAVENCIO(®) has been shown to release the suppression of the T cell-mediated antitumor immune response in preclinical models.(1-3) BAVENCIO(®) has also been shown to induce NK cell-mediated direct tumor cell lysis via antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro.(3-5) In November 2014, Merck and Pfizer announced a strategic alliance to co-develop and co-commercialize BAVENCIO(®).
BAVENCIO(®) Approved Indications
In September 2017, the European Commission granted conditional marketing authorization for BAVENCIO(®) as a monotherapy for the treatment of adult patients with metastatic Merkel cell carcinoma (mMCC). BAVENCIO(®) is currently approved for patients with MCC in more than 45 countries globally, with the majority of these approvals in a broad indication that is not limited to a specific line of treatment.
In the US, BAVENCIO(®) (avelumab) in combination with axitinib is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC). Additionally, the US FDA granted accelerated approval for BAVENCIO(®) for the treatment of (i) adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (mMCC) and (ii) patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy, or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. These indications are approved under accelerated approval based on tumor response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.
BAVENCIO(®) Safety Profile from the EU Summary of Product Characteristics (SmPC)
The special warnings and precautions for use for BAVENCIO(®) include infusion-related reactions and immune-related adverse reactions (such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis and renal dysfunction, and other adverse reactions).
The SmPC list of the most common adverse reactions in patients with solid tumors includes fatigue, nausea, diarrhea, decreased appetite, constipation, infusion-related reactions, and weight loss and vomiting.
BAVENCIO(®) Important Safety Information from the US FDA-Approved Label
The warnings and precautions for avelumab (BAVENCIO(®)) include immune-mediated adverse reactions (such as pneumonitis and hepatitis, colitis, endocrinopathies, nephritis and renal dysfunction and other adverse reactions, infusion-related reactions, hepatotoxicity, major adverse cardiovascular events (MACE) [which can be severe and have included fatal cases], and embryo-fetal toxicity.
Common adverse reactions (reported in at least 20% of patients) in patients treated with BAVENCIO(®) include fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reaction, peripheral edema, decreased appetite/hypophagia, urinary tract infection and rash. Common adverse reactions (reported in at least 20% of patients) in patients receiving BAVENCIO(®) in combination with axitinib include diarrhea, fatigue, hypertension, musculoskeletal pain, nausea, mucositis, palmar-plantar erythrodysesthesia, dysphonia, decreased appetite, hypothyroidism, rash, hepatotoxicity, cough, dyspnea, abdominal pain and headache. Grade 3-4 clinical chemistry and hematology laboratory value abnormalities reported in at least 10% of patients across studies include hyponatremia, lymphopenia, increased gamma-glutamyltransferase, blood triglycerides increased and lipase increased.
Axitinib Important Safety Information from the US FDA Approved Label
In the study of advanced RCC after failure of one prior systemic therapy, the warnings and precautions for axitinib include hypertension, including hypertensive crisis, arterial and venous thrombotic events, hemorrhagic events, cardiac failure, gastrointestinal perforation and fistula, hypothyroidism, wound healing complications, reversible posterior leukoencephalopathy syndrome (RPLS), proteinuria, liver enzyme elevation, hepatic impairment, and fetal harm during pregnancy.
Common adverse events (reported in at least 20% of patients) in patients receiving axitinib were diarrhea, hypertension, fatigue, decreased appetite, nausea, dysphonia, hand-foot syndrome, weight decreased, vomiting, asthenia, and constipation.
About ERBITUX(®) (cetuximab)
ERBITUX(®) is an IgG1 monoclonal antibody targeting the epidermal growth factor receptor (EGFR). As a monoclonal antibody, the mode of action of ERBITUX(®) is distinct from standard non-selective chemotherapy treatments in that it specifically targets and binds to the EGFR. This binding inhibits the activation of the receptor and the subsequent signal-transduction pathway, which results in reducing both the invasion of normal tissues by tumor cells and the spread of tumors to new sites. It is also believed to inhibit the ability of tumor cells to repair the damage caused by chemotherapy and radiotherapy and to inhibit the formation of new blood vessels inside tumors, which appears to lead to an overall suppression of tumor growth. Based on in vitro evidence, ERBITUX(®) also targets cytotoxic immune effector cells towards EGFR expressing tumor cells (antibody dependent cell-mediated cytotoxicity, ADCC).
Very commonly reported side effects with ERBITUX(®) include acne-like skin rash, mild to moderate infusion-related reactions and hypomagnesemia.
ERBITUX(®) has already obtained market authorization in over 100 countries worldwide for the treatment of RAS wild-type metastatic colorectal cancer and for the treatment of squamous cell carcinoma of the head and neck (SCCHN). Merck licensed the right to market ERBITUX(®), a registered trademark of ImClone LLC, outside the U.S. and Canada from ImClone LLC, a wholly-owned subsidiary of Eli Lilly and Company, in 1998.
Tepotinib, discovered in-house at Merck is an investigational oral MET inhibitor that is designed to inhibit the oncogenic MET receptor signaling caused by MET (gene) alterations, including both MET exon 14 skipping mutations and MET amplifications, or MET protein overexpression. It has been designed to have a highly selective mechanism of action, with the potential to improve outcomes in aggressive tumors that have a poor prognosis and harbor these specific alterations.
Tepotinib is currently being investigated in NSCLC and Merck is actively assessing the potential of investigating tepotinib in combination with novel therapies and in other tumor indications.
1. Dolan DE and Gupta S. Cancer Control 2014;21:231-7.
2. Dahan R, et al. Cancer Cell 2015;28:285-95.
3. Boyerinas B, et al. Cancer Immunol Res 2015;3:1148-57.
4. Kohrt HE, et al. Immunotherapy 2012;4:511-27.
5. Hamilton G and Rath B. Expert Opin Biol Ther 2017;17:515-23.
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